new discoveries for a healthy future

Sleep May Enhance Psychological and Immunological Memory

Psychological memory makes us. “If we couldn’t recall the who, what, where, and when of our everyday lives, we would never be able to manage. We mull over ideas in the present with our short-term memory, while we store past events and learned meanings in our long-term memory.”

Sleep — the natural and reversible state of reduced responsiveness to external stimuli and relative inactivity, accompanied by a loss of consciousness — supports the retention of memories of facts and events. Sleep in mammals consists of two core stages: slow-wave sleep, and rapid-eye-movement sleep, which alternate in a cyclic manner. Slow-wave sleep, often referred to as deep sleep, is important for transforming fragile, recently formed memories into stable, long-term memories.

In addition to psychological memory, there is another type of memory — immunological memory. Immunological memory is the ability of the immune system to respond more rapidly and effectively to a microbe that has been encountered previously. It is due to unique populations of immune system cells called memory B cells and memory T cells. An individual with a strong memory response to a specific microbe is said to be ‘immune’ to that microbe — this is because a strong memory response protects that individual from developing the disease caused by that microbe. Vaccines — modified forms of microbes — induce immunological memory and, by doing so, enable the immune system to respond more rapidly and effectively when encountering the original microbe.

Now, in an article published in the scientific journal Trends in Neurosciences, scientists propose that deep sleep may also strengthen immunological memories of microbes previously encountered because of either natural infection or vaccination. Indeed, in humans, long-term increases in memory T cells are associated with deep slow-wave sleep on the nights after vaccination.

Senior author Jan Born of the University of Tuebingen said in a press release: “While it has been known for a long time that sleep supports long-term memory formation in the psychological domain, the idea that long-term memory formation is a function of sleep effective in all organismic systems is in our view entirely new. We consider our approach toward a unifying concept of biological long-term memory formation, in which sleep plays a critical role, a new development in sleep research and memory research.”

The scientists propose that, although responding to different environmental events, the central nervous system and the immune system share basic functions of memory, and sleep leads to the consolidation of psychological and immunological memory. In both systems, the consolidation of memory is mediated by slow-wave sleep that suppresses certain signals while enhancing others.

In the same press release, Born added: “In order to design effective vaccines against HIV, malaria, and tuberculosis, which are based on immunological memory, the correct memory model must be available. It is our hope that by comparing the concepts of neuronal and immunological memory, a model of immunological memory can be developed which integrates the available experimental data and serves as a helpful basis for vaccine development.”

38 comments

The most interesting (and obvious) point that I took away from this article was that sleep exerts a significant influence on the immune system and immunological memory. A study titled “sleep and immune function” largely reinforces the major points that this article makes. For example, in the article lead by Dr. Luciana Besedovsky, the continual practice of shortening sleep lengths has been show to yield the constant unspecific production of pro-inflammatory cytokines, which often results in lower grade to medial cases of inflammation; however it can also result in immunodeficiency. Also, a direct correlation exists between quality sleep, and the promotion of cytokines and their ability to yield specific interactions between antigen presenting cells, and T helper cells including IL-12. Enhanced immunological memories emanating from early sleep can, according to Dr. Besedovsky’s study, come as a result of the creation of an endocrine orientation that bolster the induction of the Th1 immune response. Another aspect of this article that is supported by Dr. Besedovsky’s study are the effects of sleep on vaccinations and immunological memory. According to Dr. Besedovsky’s study, quality sleep on the night after the administration of vaccinations against Hepatitis A resulted in the yield of an strengthened and constant increase in the quantity of antigen-specific Th cells and antibody titres. However, one aspect of Besedovsky’s study that neither contradicted nor supported this article was the correlation between the sleep wake cycle, and the effects of nocturnal sleep with that of a 24 hour period of being awake, and the role of naïve T cells, inflammatory cytokines, and cytotoxic natural killer cells. With that being said, the science and literature behind these very specific subjects such as the effects of immunological and psychological memory are still in an incipient phase, and it will take some time before these contrasts can be more effectively assessed.

Sleep is one of an important physiological process. But in today world we push ourselves to work so much that we usually end up as sleep deprived. Physiologically, human recommend to sleep somewhere between 6 to 8 hours. So roughly we spend one-third of our lifetime sleeping. There is no doubt about so many benefits of sleep, especially it makes us calm, grounded and then one more gem adds to sleeping benefit here is that it boost our long term immunity by facilitating immunological consolidation. Whenever we are under any kind of stress our stress hormone i.e. cortisol level shoots up and that keep us going but on the downside, chronic upsurge of cortisol usually compromise our immunity. This mentioned conditions is true in the case of a chronic stressed individual. But physiologically to overcome this phenomenon our endocrine gland releases hormones in a pulsatile manner. As deep sleep usually keep us grounded and relax in most of day hour so immunological benefit of deep sleep really makes sense and I find the following research support these views further:

It concludes that how lower level of cortisol leads to understimulated mineralocorticoid receptors for the short period of time which contributes to an enhanced redistribution of naive T-helper cells, as a mechanism that eventually contributes to immunological memory formation. Along with it, they also mentioned how blockade of mineralocorticoid receptor leads to an upsurge in T helper cell number. Although it makes me wonder what will be the effect of chronic blockade of glucocorticoid and mineralocorticoid receptors on immunity?

There is an old saying that if you do not sleep well, you will get sick. Research has some experimental data in favor of this statement. Not getting enough sleep has a link with mental and physical health problems. Our immune system is very complex and lack of sleep is believed to lower down T cell count.http://www.webmd.com/sleep-disorders/excessive-sleepiness-10/immune-system-lack-of-sleep?page=3.
A test showed that when a person does not get enough rest, the immune system answers with an inflammatory response. This rise in inflammation can be harmful, especially when it is chronic. Heart disease, for example, is known to have inflammation as a trigger. http://www.nature.com/nri/journal/v4/n6/full/nri1369.html.
The part of the brain that does much of the work for us when it comes to our emotions is called the amygdala. It helps to keep our emotions regulated and under control. It allows us to process our feelings. During the tests, this was the part of the brain that was stressed by lack of sleep, particularly when the insomnia patients were trying to reevaluate the negative pictures. http://www.everydayhealth.com/columns/eric-cohen-breathe-well-sleep-well/lack-of-sleep-may-cause-emotional-misfires-in-the-brain/.
Insomnia and depression, the two conditions are linked. One thing that researchers have found over and over again is that those who suffer from problems sleeping often suffer from depression.
Sleep pattern adversely affects our metabolism and immune systems. The longer a person goes without adequate sleep, the more at risk they are for other chronic diseases.

Effects of Corticosteroid is wide spread but let’s focus its effects on immune system. In today’s fast pacing world lack of sleep is linked with a person’s hard work. In reality, it affects the hormone level and therefore metabolic and biochemical processes in the body. Studies show that people who are getting less sleep are prone to catch infections. Prolonged sleep deprivation causes abnormal glucose tolerance, in turn increases the risk of diabetes, cardiovascular diseases and weight gain. Glucocorticoid upregulate and downregulate up to 2,000 genes involved in regulation of the immune response. Cortisone reduces inflammation but on the other hand by doing so it suppresses immune system.
Study shows that sleep deprivation leads to decreased T Cell count and increased anti- inflammatory cytokine level, therefore suppressed immunity and higher risk of infection. When we do not get adequate sleep, C-reactive protein level rises which is also an indicator of inflammation. Not only that, it plays a role in heart disease. Cognitive ability is adversely affected due to lack of sleep.

Pratima, you are very correct with these hormones and how they affect sleep, which in return affect our immune system. During the day, our levels or cortisol concentration are decreasing to help keep minimal levels before we go to sleep. An individual who has not slept for a couple of days well have a slower rate of cortisol concentrations during the evening time than an individual was did rest. A higher rate of cortisol during the time of not getting sleep can actually lead to development of insulin resistance that lead to diabetes and obesity. Isn’t it crazy how we just linked three articles that we read together with the immune system such as the affects of sleep, obesity, and nature? With sleep, there are many cytokines involved, specifically twenty, and interleukin-1 seems to have a strong affect with rapid eye movement reduction. If we increase the levels of interleukin-1, then more rapid eye movement will occur and sleep will be obtained. This shows us that the hormones in our body work with the immune system.

Promoting the idea of getting optimal sleep is quite appealing. Epidemiologically if we look at disease pattern in different countries, it is somewhat clear that in developed countries incidence of autoimmune conditions is much more than developing countries. Although there are many hypothesis to justify this conclusion including hygiene hypothesis. But there is one more factor I see which is much common in all developed countries. It is the work culture; on the name of work culture people indulge themselves in work to the level of exhaustion. These aspects affect our life in many ways mostly affect our sleep pattern and usually leads to insomnia. Along with it, erratic and unhealthy eating habit, usually seen with this lifestyle also contributes to obesity. Then obesity usually affects sleep quality by sleep apnoea. So overall, work related stress somewhat leads us to sleep deprivation and that further go for many pathologies including autoimmunity. I find this idea quite interesting and find similar finding in the following research:

Here author states that how insomnia induced lymphopenia, which leads to dysregulation in immune responses and autoimmune reactions. This finding is further strengthened by the fact that most cases of autoimmunity present with lymphopenia. It makes it further clear that how deep sleep is important for the healthy immune system.

Sleep is a very important physiological process for all living organisms. We all know that a sound night sleep of 6 – 8 hours is necessary for proper growth, metabolic processes, and many other important biological functions in humans. Lack of sleep can be related to many disorders like depression, obesity, diabetes, immunological changes etc.
Sleep deprivation is associated with increased levels of certain inflammatory mediators during daytime and these are associated with increased cardiovascular events. In a study of young adults, it was found that deprived sleep in last night could increase daytime secretion of IL-6, which results in fatigue and somnolence in the next day. In a similar study conducted in persons suffering with chronic insomnia, a shift in the secretion of IL-6 and TNF from nighttime to daytime was observed.
This change in the secretion of IL-6 and TNF are associated with daytime fatigue, decreased productivity and performance in an individual suffering from insomnia. This is also sometimes combined with a 24 hour hyper secretion of cortisol, which is also responsible for fatigue and sleepiness in the day time.
Reference:
Laila AlDabal and Ahmed S BaHammam, Metabolic, Endocrine, and Immune Consequences of Sleep Deprivation, The Open Respiratory Medicine J. 2011; 5: 31–43.

The findings in this comment are quite interesting. Understanding the immune system’s direct disposition during insomnia could aid in finding therapies to help with the disorder. Being an insomniac, I am interested in seeing and reading more research targeting the cellular level involved in the disorder. I experience the daytime fatigue and low performance during episodes of insomnia. The fact that IL6 cells are normally seen during infection and after trauma could lead to the answer of what is going on in the body of patient’s suffering from insomnia. The body is undergoing a great deal of stress and this is definitely linked to the onset of depression and irritability. Sleep is definitely a key player in overall health and is highly important in the immune system’s ability to fight off infections/invasions.

Sleep, Sleep, Sleep! It seems to be a key part of many health related or psychological issues. Sleep has been long said to be a main ingredient in the body’s immunological response. When I get a cold, I here the statement, “Get some rest” repeatedly, and I can concur that when I get adequate rest, my overall health seems to improve and I can detect that my immune system is at its best. Our body remembers different pathogens that it is has encountered, which may explain the fact that I am nearly unsusceptible to my “boyfriend’s” colds anymore (maybe it is always the same strain).

Sleep improves the immune system by providing grounds for developing better immune memory. Your body encounters pathogens and the ideal system would make memory T cells based on this encounter to make later invasions easier to combat. Memory cells can last for months to years, and is the gist of the underlying mechanism of vaccinations. Slow-wave or deep sleep is necessary to transform fragile memories to stable memories; therefore, it is safe to say that without adequate sleep your body is at risk.

Deep sleep is definitely “The Holy Grail” of sleep; it is the only sleep that allows me to feel well rested and not exhausted. I think that the level of unconsciousness allows the body time for repair, because of the level of rest, and at this point, there is little to no psychological or physical activity going on and the immune system can “catch-up” on its workload. Being able to achieve a “psychological type of rest”, allows the body to retain / remember many things that it has been exposed to. Graduate studies have further informed me that sleep is the key to retaining the knowledge of the MANY things I am learning. As a graduate student, you are faced with so many challenges and so much knowledge that it is nearly impossible to retain without studying and sleeping. When cramming for exams I find myself not getting the rest I need before testing. Each time, this results in a “blank out”, I knew the material, but it has selectively exited my brain. Challenging, intense, and stressful to say the least, I believe that rest/sleep could be the answer to a successful completion of my second graduate degree and a successful immune system.

The point you make about not being able to perform as well on exams if you have not slept enough resounds with me. The fact of the matter is that, as Grad students, we have basically signed ourselves up in a competition of who can sleep the least. At first it sounds ridiculous, but if you really start pondering about what we do, you’ll see that I am right. As students, we praise ourselves for being able to survive full weeks on nothing but coffee and the impending doom of not doing well on our tests. At any given moment (especially now that the finals period is coming up) you are likely to hear conversations between students that go along the lines of “I think I am going to have to pull an all-nighter to get through all this material” and “I have had six RedBulls in the last five hours, but I finished writing my research proposal paper”. In any other context having to stay awake so long would be considered cruel and unusual punishment, so why is it so commonplace in academics.

I think one of the major problems lies in the atmosphere of increased competition that academia is now subject to. There is no more “learning for the sake of learning”. Everything has to have a reason; every class has to lead to some sort of benefit, and every day you spend in lab should be in the efforts of getting one piece of data that will land you a grant or publication. Wile all this extra effort is fantastic for the individual lab and the reputation of an Institution, as a whole, the negative repercussions fall directly onto the person making these sleep sacrifices. I am more than guilty of spending full weeks working on twenty-odd hours of sleep and every time, without fail, I always feel under the weather for days, afterward.

One of my lab mates, while under a combination of stress and overworking succumbed to four-weeks of recurring strep-throat infections and a bad case of conjunctivitis. What should be a cause for concern was brushed off as “oh, it was just normal, end-of-the-semester, four-week sickness”. This is where I feel that offices and committees designed for student welfare have dropped the ball. You have a whole student body for which you are theoretically responsible for and you are allowing practices that are causing them to fall ill. However, as a community (students, professors, administrators, etc) we are so conditioned to see it as a normal occurrence that we don’t think to do anything about it. I think that a change in how academia is built to demand and motivate its students should be reconsidered so that we might not only get better results (because a well-rested investigator gets better data), but decrease the frequency of illnesses and in so reducing the costs of student healthcare. It’s a win-win.

With the established connection between sleep and overall quality of health, I would be interested in fluctuating the variable of time spent sleeping in order to establish a range of effectiveness. Humans usually sleep as a 6-8 hour session starting at night and ending the next morning. This form of sleep is considered monophasic. I would be interested to assess the immunological impacts from multiple other methods of sleep, from biphasic to polyphasic. Biphasic would likely be two sessions of 4 hour sleep cycles, and polyphasic patterns can range from multiple 2 hour naps a day to naps as short as 15 to 30 minutes. The Uberman sleep schedule allots for six 20 minute naps a day. Given the wide variability of sleep patterns, does immunological health suffer as we spend less and less time in slow-wave sleep, or does the act of merely entering slow-wave sleep for a mere 10-15 minutes per sleep session allow for the formation of the necessary immunological memories? Are we wasting a third of our lifetime on a process that could be completed in a mere 20 minute nap?

I personally do not sleep more than 6 hours in one night. Why you ask? I was diagnosed with chronic migraines at the age of 12. For some reason if I sleep more than 6 hours in a day, it is a migraine trigger. This includes naps. I don’t take any unless I want a debilitating headache. I find the 20 minute nap theory intriguing personally. If I could find a way to get adequate sleep in little enough time to support my neurological memory, immunological memory, and keep migraines at bay then that would absolutely be the answer. I mentioned before in class that I have chronic sinus infections due to a cyst in my sinus cavity. Maybe if I was able to sleep more my immunological memory would increase against these sinus infections.

Whether monophasic, biphasic or polyphasic? What is the answer? Despite being calmest experience, the nature of sleep always arouses curiosity among scientists. About duration and type of phase, every case is individualistic. But I still believe monophasic sleep seems like a practically most viable option. Why is it so. Our whole social structure designed for early riser and one who can do their job throughout the day. So apart from being social and practically viable, if we look at the physiological aspect of monophasic sleep, they seem quite appealing.

Our one sleep cycle is comprised of 4 stages. First three being part of non-REM, whereas the last stage known as REM sleep. REM sleep comprises most of our deep sleep. In most of REM we use to dream, it seems like prosaic but it is most important part of sleep. Although one sleep cycle approximately last for 90 minutes, so longer back to back sleep cycles make more sense than the fragmented pattern as in polyphasic sleep. If we are going with polyphasic sleep pattern, we may be spending lesser time in deep sleep compare to monophasic sleep. So overall chronically spending lesser hours in deep sleep may not be that beneficial for memory consolidation

According to a study done on medical students biphasic sleep elicited the best results when compared to their academic performance on a midterm. This, however, was not from sleeping two times for 4 hours each. They found that sleeping for a longer duration during the night and then taking a shorter nap during the day was optimal for retaining information and maintaining alertness. Students that slept in a polyphasic manner actually performed the worst, more so than those that were monophasic. Their study agreed with the current accepted hypothesis that REM sleep is essential to memory formation, which you can’t undergo when sleeping for 90 minutes or less each time (Saeed, Hasan, & Atif, 2015). If formation of psychological memory is also tied to formation of immune memory as this post suggests, then the same must hold true. Couple this with the immunological impairment and/or over reactivity studies in sleep deprived states others have mentioned in this thread I think it is safe to say that sleep is essential to a healthy immune system.

In a study published in the Journal of Sleep Research, researchers determined that once removed from sociological and physical stimuli, during what is called a disentrainment phase, all subjects from a variety of age groups resorted to a polyphasic sleep pattern. This is believed to be a primitive pattern established by humans before the advancement of civilization, as nearly all animals in the animal kingdom exhibit the same sleep pattern. While this primitive sleep schedule may result in the inability to handle the modern day mental rigor of something as strenuous as medical school curriculum, I would not find it far fetched to theorize that this polyphasic sleep pattern provides enough REM sleep for a biological entity to bolster the immunological defenses pre-civilization humans would require as they foraged, braved the elements, and endured the wilderness.

After reading this article, I thought it made perfect sense that sleep enhances psychological memory. However, I was a bit skeptic to the thought that sleep had any effect on immunological memory. Furthermore, if sleep did have any effect on immunological response, I did not think it would be significant. Researchers, suggest that individuals should get 6-8 hours of sleep per night. However, being a full time Grad student and full time worker, I only have the luxury of sleeping 4 hours a night. Yet, I am rarely ill. Then I thought about my classmates who probably have a schedule similar to mine and thought they do not appear to be sick often either. As noted in the article, sleep leads to the consolidation of immunological memory and the consolidation of memory is mediated by slow-wave sleep that suppresses certain signals while enhancing others. This prompted the thought that deep sleep may only have to occur for shorter period of time to consolidate memory and therefore it does not matter the amount of time you sleep, just so long as deep sleep occurs for an individual’s consolidation of memory. Given that most individuals are able to achieve deep sleep at least once per day, I think environmental and social factors have a deep impact on immunological memory.

I find your points interesting, but I don’t know that I would say that sleep is a waste of time. It’s been shown that sleeping during the night is important to the production of pro inflammatory cytokines and naïve T cells. Additionally, it’s also been shown that periods of nocturnal sleep have an enhancing effect on the cytokines that promote antigen presenting cells’ interactions with T helper cells. This interaction between antigen presenting cells (APCs) and T helper cells is critical for their functioning. The study that the main post references shows that most of the immunological effects happened during periods of slow wave sleep that do occur during short periods of sleep, however other studies have shown that these process rely on periods of nocturnal sleep in order to occur. I also think that as great as it would be to only have to sleep in 20-minute increments it would prove to be problematic for other body systems. This increased cytokine activity also appears to be linked to high levels of growth hormone and prolactin as well as low levels of stress hormones – these conditions would only be present during longer periods of sleep.

I think you make some very valid points about the reality of what now defines a “full night” of sleep in our current situation as graduate students. I agree with your statement regarding environmental and social factors and their role on immunological memory. Some experiments that lend some support are the Wessel M. A. van Leeuwen article “ Sleep Restriction Increases the Risk of Developing Cardiovascular Diseases by Augmenting Proinflammatory Responses through IL-17 and CRP” and the Gonzales et al article below which looked at the effect stress had on mice subjects immunological response to a primary and secondary Streptococcus pneumoniae infection. The Gonzales research showed that stressed mice actually had a better survival rate during the primary infection when compared to the non-stressed mice. In the van Leeuwen article, they actually saw an increase in peripheral blood mononuclear cell proliferation in the sleep deprived subjects in comparison to the control test group. This lead to the suggestion that T cells in sleep deprived people, compared to people with normal sleep, are primed and after non-specific stimulation will lead to a more efficient response. Unfortunately, the stressed mice in the Gonzales study had an extremely reduced survival rate during the secondary infection and, in conjunction with the van Leeuwin study results, lead to the conclusion that “over activation of effector cells may enhance immunity and help the individual to survive through extraordinary conditions in the short term, but prolonging this situation leads to inflammation, and tissue injury.” So maybe you won’t get sick now but there is the possibility of future illness, probably when you’re not even stressed. That would be our luck.

Good Point Bart. I too have heard that 6-8 hours is what you absolutely need for your body to replenish its energy or even immune system. However, after reading this article it makes more sense to me the reason why that amount is recommended. It takes many people a while to get to the deep sleep state, whereby memory lymphocytes are increased and more prepared to respond to re-infecting pathogens. It is easier to assure that this stage of sleep is attained when you give yourself more time to sleep. Hence, it may not be completely necessary to get that amount of sleep it is just more likely that you when you do you would have reached the deep sleep state and experienced a sufficient amount of it in order to boost adaptive immunity. Consequently, I would agree with you that shorter amounts of sleep could lead to the same amount of immunological benefit.

first of all, epidemiologic investigation requires a sample pool larger much more than a class with less than 50 individuals. It’s inadvisable to consider the appearance on one person as a significant, representative phenomenon. It’s easy to accept that a good sleep may improve immunological memory, since we’ve all agreed that good sleep can improve body function, part of which is the immune function, and immunological memory is part of the immune system. Truth is no one could ever conclude how significant the influence of sleeping is on the function of immune system, for which is under the influence of multiple factors as you mentioned. The study of immune system and its relationship to other systems in our body has just started, and we need more pieces of evidence to put together to get the whole picture.

College students are one of the most sleep-deprived populations. There is a direct correlation between lack of sleep and lower GPAs because of how it affects concentration, memory, and the ability of an individual to learn. Sleep deprivation leads to an “alteration in the neurophysiological and endocrine systems, rendering all learned and practiced events during the period of sleep deprivation moot.” There is a huge percent of student population that suffer from some kind of sleep disorders which in turn prevents them from getting the optimum hours of sleep needed. A study of Neurophysiological Effects of Sleep Deprivation in Healthy Adults “has shown that people suffering from total sleep deprivation have an increase in dopamine output and a decrease in cortisol, thereby requiring an increase in a combined effort of production from the prefrontal and limbic cortical regions. Despite the increase of activity in the brain, individuals still suffer from decreased cognitive performance,” such as lack of reasoning, attention, and retaining memories. Therefore, proper amount of sleep is imperative for the proper functioning of our immune and body systems.

I always seem to get sick when I don’t get enough sleep. However, I’m not sure I blame my sickness all on my sleep. I believe stress is a huge factor too, or at least the stress combined with a lack of sleep, makes me sick. Nonetheless, I’ve always heard of studies that say a lack of sleep suppresses the immune system. But is it a lack of sleep, or not getting the type of sleep we need? Perhaps inefficient sleep. I feel that stress is the stem of the sleep problem. Whenever I have something important such as an interview or test the next day, I wake up often throughout the night. Maybe I have too much anxiety, but stress impacts my sleep quite a bit, in turn affecting my immune system. For me, and a lot of other people, stress is the stem of the cause of my immune system going awry. Not only do I believe getting deep, REM sleep is very important, but also exercise. I have seen studies showing exercise helping the immune system as well. Exercise helps people sleep better, eat better, and have a healthier immune system.

A recent study that came out September 2015 showed that shorter sleep duration measured behaviorally using actigraphy prior to inhalation of rhinovirus was associated with increased susceptibility to the common cold. This was quite obvious, but shows the importance of sleep and the common cold (Prather, 2015).

I am curious to find out how sleep impacts the immune system of those that are immunocompromised, whether autoimmune diseases or those undergoing radiation. I assume those that have immune deficiencies critically need sleep. However, would they benefit from more sleep? I’ve seen studies that show how healthy people getting too much sleep (Over 9 hours) can negatively impact the health. In immunocompromised individuals, would more sleep that usual be beneficial in protecting themselves?

As it mentioned in the last comment, about the effect of stress on the sleep and pattern of it. I feel like there are so many agonist-antagonist pairs in our body and sleep-stress is one of them. This symbolic interaction came in my mind by looking at the pattern of sleep and stress. They are relative to each other. If one sleep sound that keep stress at bay, and it is another way around too. So it is well known how prolong stress elevate the level of stress hormone i.e. cortisol in our body. During chronic stress elevated cortisol level apart from maintaining our whole metabolism, also impairs our immune system by suppressing it. In short, stress suppresses our immunity and it seems logical that it can affect the immune cells consolidation.
While when one is well rested, they are immune to stress and can perform at their best. So as the deep sleep make us well rested and boost the androgens level too, which further make our immunity better. So overall it makes sense that how deep sleep not only makes us relax and consolidate our short term memory but promotes immune cell consolidation too.

I find this article fascinating because it not only describes the overall significance of sleep to our immune systems but it also reveals how the effect of sleep on our immunological memory can be the key to discovering new breakthrough vaccines. As described in the article, sleep was long thought of as merely benefiting ones psychological memory, not the immunological memory. However recent studies support the claim that sleep actually generates longer lasting T and B lymphocytes that are better equipped to respond quicker and more effectively to microbes that are re-introduced to our bodies. This critically explains why a large percent of the global population’s health and immunity become more compromised as they get older because they get less sleep commonly due to stress, work, raising children and other adult related issues most people will experience. Interestingly, it is the deep slow wave stage of sleep that is most affected by sleep as this is the period when more memory T cells are generated. Consequently, a person who is experiencing more quality sleep will have this stage’s functioning enhanced leading to overall better immune memory and a more specific response to that particular pathogen. This process can be instrumental in understanding how devastating viruses such as HIV and malaria establish such a strong ability to evade and prevent adequate memory formation in lymphocytes. HIV in particular is known to directly attack and infect T helper cells which results in decreased immune function and memory (Virology Journal). This will severely affect the ability of sleep to help with the memory of these very cells that are infected. Improved knowledge of how these viruses manifest into disease can pave the way for superior vaccines that will save many lives. It is great to know how one hidden way that adaptive immunity is strengthened could now be facilitated in such a transformative manner!

In the older days, they always use to say that the best cure for sickness is rest and sleep. The connection between sleep and immune system has always been curious but recently started being investigated. Even though they affect each other, it is hard to prove that sleep loss will change the immune function or the immune system can change sleep. Twenty cytokines have been studied and known to determine effects on sleep. Specifically, interleukin-1 (IL-1) and tumor necrosis factor (TNF) that have been consistently mentioned in these posts play a role in the regulation of non rapid eye movement sleep. Studies show that antagonizing the IL-1 or the TNF can reduce spontaneous non rapid eye movement sleep. The opposite also shows that when antagonists are blocked the IL-1 and TNF systems increase as well as non rapid eye movement sleep. These cytokines can change properties of neurons in the brain especially in the regions of sleep.

Studies have thought that sleep can be a element of acute phase response to infection and functions in host defense. Preston and colleagues showed that there is an increase of white blood cells with more total sleep in a cross of 26 mammalian species, which says that with more sleep they should be more immunocomptent. Evolution has showed that organisms have evolved over time and adapted to their surroundings. Organisms like annelids, mollusks, arthropods and protochordates have IL-1, IL-6, TNF, and transforming growth factor (TGF)-beta like molecules. Drosophila has been studied in details because of their simplicities as organisms and similarities to humans. They have the gene for the NF-kB like transcription factor, called relish that helps with sleeping more. Flies that don’t have as much relish sleep less and also relish will increases when there is sleep deprivation. This transcription factor is import to host defense because they play a role in cytokine transcription. Sleep deprivation increases the activity of relish, which in return helps for fighting infection. Flies without Relish gene do not go through acute sleep response and are quick to infection.

How important is sleep? I like to look at it like a stress-reliever mechanism. It is extremely important and needed by our bodies. As adults, we go to work and everyone is busy in their own lives. Once we come back home, extremely tired, all we look forward to is our bed (and possibly food, if you’re hungry) and we’re off to sleep only to wake up and start the routine all over again. But let’s stop and think about our immune system. From the day we are born to the day we die, our immune system is consistently and efficiently at work, remembering all the little details and storing it in forms of memory. It’s like us, psychologically saving all memories in order to remember things long-term. I can only imagine the struggles if our immune systems or our bodies were unable to store these memories. Studies on sleep, in the previous years, have collected and maintained evidence that showcases the ability of sleep to support the formation of long-term memory. The study, referenced in this blog, specifically, is very interesting because it makes a great point. If both, psychological and immunological, domains have similar functions (that of storing memories), sleep may aid in communication between the two systems at some point. Their mechanisms may differ but their “end goal-“that of storing events as long-term memory remain the same. It has been shown that our sleep is regulated partly by immune cells, such as cytokines. A study finds that after sleep, vaccination against hepatitis A doubled the frequency of Ag-specific Th cells and increased the Th1 cytokine production, facilitating an immune memory. These effects were associated with the SWS or what we like to call “deep sleep.” So my question is what is happening in our body while we sleep that this same process doesn’t occur as effectively while awake? We know that like the nervous system, immune system and psychological system take advantage of the “offline conditions” while we sleep to facilitate effective immune as well as psychological response. I think further work can be done on exploring these “offline conditions” to maybe enhance the psychological and immunological response while awake?

I really appreciate the ideas that how offline mode facilitates memory consolidation of immune cells; how immune cells and interleukins vary with circadian rhythm. As that how numbers of undifferentiated T cells and the production of pro-inflammatory cytokines shows peaks during early sleep while circulating immune cells like natural killer cells, anti-inflammatory cytokine activity upsurge during wake hours. Although it is a difficult task to pinpoint that how deep sleep affect immunity and circadian rhythm but then there are few studies which show how sleep influences some cytokine that facilitate interactions between APCs and T helper cells. It is not an exaggeration to say that if the level of circulating immune cells is higher in waking hour then why not memory cell consolidation may be faster in deep sleep. Although this claim needs further validation, but in the context of the following paper: doi:10.1007/s00424-011-1044-0 it makes sense.
Although immunity consolidation may happen due to many interactions, but few seems quite prominent as immune system directly regulated by the autonomic nervous system and endocrine interactions. This result is further encouraged by the fact that prolonged wakefulness in mice is associated with disturb immune function or even immunodeficiency. During deep sleep level of growth hormone and prolactin rises whereas cortisol and catecholamine dipped. This endocrine regulation leads to an overall decrease in sympathetic activity; so unopposed increase in parasympathetic tone facilitates the memory cell formation from existing T and B cells. Also, consolidation of immune function in deep sleep is contributed by following factors such as an enhanced production of IL-12, increase in Th1/Th2 cytokine balance, an increased proliferation in Th cell etc.
Reference: Besedovsky L, Lange T, Born J. Sleep and immune function. Pflugers Archiv. 2012;463(1):121-137. doi:10.1007/s00424-011-1044-0.

The nervous system is the most complex and least understood organ system of them all. It is known that the Nervous system and the Immune system communicate with each other, given the presence of immune cells defending against organisms and fluid containing soluble immune mediators in the brain and spinal cord. Originally, there was no evidence lymphatic vessels were present in the central nervous system. Therefore, researchers were unsure how these cells were able to cross the barrier, since the blood brain barrier is highly impermeable. However, after further investigation, it was revealed that immune cells and fluid are produced by deep cervical lymph nodes. Given these findings, I think it is important to investigate the correlation between certain nervous system diseases such as multiple sclerosis and Alzheimer’s to identify if there is any lymph vessel damage associated with these diseases. I am sure lymph vessel damages occur with age, but I would also want to identify environmental and social factors that could be associated with increase damage to these blood vessels. For example, I would want to identify if alcohol or smoking promotes further damage of the lymphatic vessels.

I may be wrong, but I don’t think the lymph vessels are part of the CNS. A study I read on lymphatic drainage of the brain and the pathophysiology of neurological disease states that cerebrospinal fluid drains through the cribriform plate and nasal mucosa down to the cervical lymph nodes (animal model). However, it appears that neither antigen-presenting cells nor lymphocytes are drained this way. They did show that blockage of lymphatic drainage by interstitial fluid and solutes from the brain could disrupt homeostasis of the environment which could contribute to different kinds of neuronal malfunction. Facilitating the lymph drainage of amyloid-beta could provide a therapeutic strategy for Alzheimer’s disease. High concentrations of Abeta in the brain causes Alzheimer’s to progressively get worse. I would be interested to see if they could use this for other degenerative neurological diseases too.

A study on enhancing versus suppressive effects of stress on immune function shows that stress has bidirectional effects on immune function. Acute stress experienced at the time of primary and secondary exposure resulted in an enhanced response. In contrast, chronic stress was shown to suppress immune function. The levels of corticosterone, epinephrine, and norepinephrine play a role in determining whether or not it is acute or chronic stress.

These hormones appear play a role in the connection between neurological and immunological memory consolidation. The locus coeruleus & norepinephrine reticular activating system is involved in attention, arousal, sleep-wake cycles, as well as learning and memory. In addition, the raphe nuclei & serotonin reticular activating system is active during slow wave sleep. High stress or corticosterone levels disrupt the body’s normal Circadian rhythm, which I believe would affect memory consolidation in the nervous system. I also believe it affects immunological memory, but I didn’t see any studies supporting that yet. I think there is a mechanism that links the immune system and nervous system in the sense of memory consolidation, but it will take more research to discover it.

This article is not something over worked people should read since it may lead to sleepless nights worrying about how much damage we are doing to ourselves because of our lack of sleep! Vicious cycle indeed. Add to this the research discussed in Wessel M. A. van Leeuwen et al. “Sleep Restriction Increases the Risk of Developing Cardiovascular Diseases by Augmenting Proinflammatory Responses through IL-17 and CRP” and we are in for a disease ridden life. Their research showed that, in human subjects, a five night sleep restriction of only four hours in bed per night led to an increase of cytokines IL-1B and IL-6 which increase the expression of the pro inflammatory cytokine IL-17. The levels of IL-17 did not return to normal levels even when followed by a two night recovery phase of eight hours in bed per night. This cytokine has been linked to sustained tissue damage in the brain, heart, lung, intestines and autoimmune disease development. The researchers did acknowledge that due to the short duration of their experiment, long term immunological effects of sleep deprivation could not be definitively concluded. However, much to my dismay, the researchers concluded that trying to compensate for previous sleepless nights with longer sleep times after will not entirely reverse the immunological effects and that this cycle of sleep deprivation and recovery could lead to an increased risk of cardiovascular disease.
References:
Wessel M. A. van Leeuwen, Maili Lehto, Piia Karisola, Harri Lindholm, Ritva Luukkonen, Mikael Sallinen, Mikko Härmä, Tarja Porkka-Heiskanen, Harri Alenius, “ Sleep Restriction Increases the Risk of Developing Cardiovascular Diseases by Augmenting Proinflammatory Responses through IL-17 and CRP,” PLoS ONE 4(2): e4589. doi: 10.1371/journal.pone.0004589http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0004589

I’ve always thought that sleep is medicinal and good for the health. Reading this article confirms my thoughts because of its co-relation of sleep and the immune system. Sleep being associated with memory immune cells is quite interesting because sleep plays a significant role in creating memory cells. According to this article deep sleep this may strengthen immunological memories of microbes previously encountered because of either natural infection or vaccination. Brain has to create a memory for the microbe to recognized in terms of future encounter. How can the creation of memory be achieved? Sleep. Why deep sleep? Deep sleep transforms recently formed memories into stable long-term memories. Confirmation of this mechanism is evident in fevers. Fever is a way our body combats infection. Fevers tend to rise at night when we are asleep.
This is also confirms the connection between the weak immune system and lack of sleep. Studies have shown that our T-cells go down and our inflammatory cytokines go up when we deprive ourselves of sleep. This makes us more susceptible to infections.
I totally understand this article and agree with its findings. The question I have is, is there an aspect of the immune system involves rapid-eye movement sleep?http://www.webmd.com/sleep-disorders/excessive-sleepiness-10/immune-system-lack-of-sleep

I firmly believe that sleep does enhance psychological and immunological memories. The sleep cycle of humans is directly related to our circadian rhythm. This rhythm mediates human behavior based on daily cycles of light and dark. Many physiological and biological processes are coordinated by circadian rhythms. Most physiological functions are altered based on these circadian rhythms where light and dark cycles affect rhythms. All cells in the body have a circadian rhythm. The most important cells related to the circadian rhythm are those in the suprachiasmatic nucleus (SCN). The SCN is knowns as the body’s “biological clock”. The SCN basically controls the cycle of all the other cells of the body (even though each individual cell has its own clock). We need the SCN because naturally our body’s cycle can range from 24 to 25 and a half hours depending on the individual; the SCN is needed to keep the body’s cycle at 24 hours. [1] A study evaluating circadian control of innate immunity in macrophages by miR-155 targeting Bmal1 stated that previous results suggested that there may be a molecular clock that regulates the mammalian immune response, but the mechanism was unidentified. The researchers found that an miRNA was a key regulatory part of the circadian function; it provided the mechanism for which the circadian clock controls the immune response. The mechanism involves potentiating inflammation in macrophages as well as targeting BMAL1 which is a clock gene. The researchers were able to conclude that affecting a clock gene through rhythm suppression would affect the innate immune response. [2] Different clock genes that are related to psychological and immunological memory enhancement are activated based on environmental cues such as the dark and light cycle, hence why it is crucial that we follow the light and dark cycles that our body needs instead of diminishing the lenghts of the cycle.

Today many people suffer from sleep deprivation, which has serious health effects. Sleep is associated with many neurological, physiological and immune functions. Many inflammatory cytokines like interleukins (IL-6, IL-1), tumor necrosis factor are major contributors of sleep disturbances. Sleep deprivation also contribute to regulate the levels of the cytokines, which has found to cause many gastrointestinal disorders. In other words patients with gastrointestinal disorders are found to suffer from sleep deprivation and imbalance in their sleep wake cycle.
Inflammatory bowel disease is a chronic inflammatory mediated gastrointestinal disorder. The patients suffering from this disorder was found to have poor sleep habits. Sleep disturbances are associated with liver diseases. Cirrhotic patients are found to have induced sleep wake cycle reversal. Disturbed sleep pattern was observed in patients with Hepatitis C. Although the exact mechanism behind these are unknown it is thought that elevated levels of IL-6 play a major role. Similarly night shift workers are found to have high risk in developing colorectal cancer.
References:
Tauseef Ali, James Choe, Ahmed Awab, Theodore L Wagener, and William C Orr, Sleep, immunity and inflammation in gastrointestinal disorders, World Journal of Gastroenterology. 2013 Dec 28; 19(48): 9231–9239.

In a previous class parasitology I remember learning about African sleeping sickness also know as African trypanosomiasis, a parasite that invades that circulatory and the lymphatic system then highjacks the circadian rhythm causing patients to sleep during the day and stay awoke during the night. African trypanosomiasis activates the immune system innate response causing inflammation at the site of the tsetse fly bite then after a few days the adaptive immune system causes fever, total body itching and extreme swelling of the lymph nodes. Once in the circulatory system it can cross the blood brain barrier causing the neurological phase. I believe part of the symptoms of the neurological phase is due to the disturbances of sleep leading to the psychological and behavioral changes such as erratic behavior, anger, irritability and confusion often seen in patients with African trypanosomiasis. In addition, studies have shown that mice infected with African trypanosomiasis causes reduced bone marrow, B-cell maturation and loss of antibody mediated immunity which is found when vaccination induces memory B-cell responses (1). Another experimental study with African trypanosomiasis researchers found that follicular B-cell destruction and memory B-cell impairment is mediated by IFN-γ (2). After reading this article I believe the sleep disturbances seen in African trypanosomiasis contributes to loss in antibody mediated responses. In addition, the loss of memory B-cells and memory T-cells due to lack of sleep could be mediated by cytokine IFN-γ in cases other than African trypanosomiasis.

This article once again demonstrated the idea that human body with multiple organs and systems should be considered as a unified whole when doctors and medical researchers are investigating diseases and treatments that may affect people’s health in many directions. For example, the metabolic stress caused by sleep deprivation is now confirmed as the cause or precipitating factor of multiple disease and disorders such as hypomnesis and immune dysfunction. This idea also suggest that when developing new treatments against the systemic diseases, such as SLE, brain infection, chronic inflammation and cancer, researchers should switch their direction from developing drugs with single main-component targeting only the nidus to creating a combination of treatment regulating multiple tissue and cell functions to be more effective and achieve better result.

Your comment makes me think of why I want to be an Osteopathic Physician (DO), and not an MD. For example, if you go to a primary care MD physician often for an illness (nothing too serious), they will likely treat you with a medication, or tell you to let it run its course. If you go to a primary care DO, they should and usually will determine why you are getting sick. DO’s try to get to the root cause of an illness, treating the whole body, not just symptoms like MD’s usually do. If someone keeps coming in with colds and flu’s, obviously their immune system is compromised/low. So, why not get to the cause of why. Is it that they work in a school, or don’t wash their hands regularly, or work in a hospital, or just don’t get enough sleep? Well, when a DO asks these questions and determines that they do not get enough sleep; the physician has the chance to inform the patient to get more sleep, because it is important for their immune system. If the patient is sleep deprived, the physician should alert them that if they continue to not get enough sleep, serious things can happen to them, and even an autoimmune disease. I totally agree that it is important for primary care and internal medicine physicians to not just treat patient’s symptoms, but to treat them as a whole person and treat the whole body. It’s not that researchers should focus on developing drugs to treat multiple tissues or systems, but that physicians need to treat their patients with a whole body approach and seeing what is truly wrong with them and needs to be changed.

Shawn, I agree with your opinion on the differences between a DO and an MD. My personal experience with some health problems actually made me lose interest in becoming an MD. I always felt that my MDs were quick to link symptoms to a specific illness and then provide medicine/treatment based on that. My experience with DOs has been that they also provide medicine/treatment, but they try to find the root of the problem and address that. After seeing many different doctors and being given many different treatments I was distraught based on how I was evaluated and treated by MDs. However, I have a lot of respect for all careers in the medical field as the main goal is to help sick people get better. I hope in the future, MDs and DOs can learn from each other and work together to provide a better standard of care. I personally decided that the research field would be best for me after this experience.